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Antibody gene transfer for HIV immunoprophylaxis

Synopsis

The search for a safe and effective HIV vaccine has frustrated scientists since the discovery of HIV-1 almost 30 years ago. Attempts to design a vaccine by conventional means have either failed or provided only modest, short-lived protection. While scientists continue their efforts to improve the efficacy and duration of protection of a vaccine that harnesses the natural immune system to provide protection, alternative strategies that might prevent infection must also be pursued.

Antibody gene transfer is a novel vaccine approach that bypasses the natural immune system response that was the target of all previous attempts to develop an HIV vaccine. Because this approach skips many of the steps in the usual path followed by vaccine developers, it has been described as using a “leapfrog strategy.”

By transferring the genes that encode for potent, broadly neutralizing antibodies that block HIV infection – antibodies that are produced too late and in insufficient quantities during the course of natural infection to stop HIV from gaining a foothold – scientists have shown that they can protect rhesus macaques from SIV infection. The excitement generated by this new approach has revived interest in passive immunization and other antibody-based therapy options to prevent HIV.

This strategy has also renewed interest in the use of adeno-associated viruses (AAV) as vectors. These small, ubiquitous viruses are structurally simple and versatile. Gene transfer vectors based on recombinant AAV have generated excitement in recent years as potential agents for a wide assortment of human applications.

The symposium discusses the latest developments in the use of gene transfer technology for in vivo HIV neutralization and the scientific challenges that lie ahead. It also addresses the challenge of convincing funders and policymakers that the gene delivery of antibodies is a valid strategy for vaccine researchers to pursue and one that should not be held back by definitions of what constitutes a “vaccine.”